(3R,4S)-4-(tert-butyloxycarbonylamino)-3-fluoro-5-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)pent-1-ene | 1020409-90-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3R,4S)-4-(tert-butyloxycarbonylamino)-3-fluoro-5-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)pent-1-ene
• 英文别名: tert-butyl N-[(2S,3R)-3-fluoro-1-[(2S,3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)oxan-2-yl]oxypent-4-en-2-yl]carbamate
• CAS: 1020409-90-8
• 化学式: C₄₄H₅₂FNO₈
• 分子量: 741.897
• InChiKey: JGHJBWYJYXBPIQ-OPXTYKRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  54
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  93.7
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3R,4S)-4-(tert-butyloxycarbonylamino)-3-fluoro-5-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)pent-1-ene 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 sodium acetate 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 31.25h， 生成 (2S,3R)-3-fluoro-2-hexacosanoylamino-1-(α-D-galactopyranosyl)heptadecane
  参考文献：
  名称：

  3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

  摘要：

  We propose here the synthesis and biological evaluation of 0 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

  DOI：

  10.1021/jm201368m
• 作为产物：
  描述：

  (2S,3R)-2-(tert-butyloxycarbonylamino)-3-hydroxy-1-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosyl)pent-4-ene 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以35%的产率得到(4S,5S)-(2,3,4,6-tetra-O-benzyl-α-D-galactopyranosylmethyl)-5-vinyl-1,3-oxazolidin-(3H)-2-one
  参考文献：
  名称：

  3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

  摘要：

  We propose here the synthesis and biological evaluation of 0 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.

  DOI：

  10.1021/jm201368m

文献信息

• 3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice
  作者：Julie Hunault、Mette Diswall、Jean-Cédric Frison、Virginie Blot、Jézabel Rocher、Séverine Marionneau-Lambot、Thibauld Oullier、Jean-Yves Douillard、Stéphane Guillarme、Christine Saluzzo、Gilles Dujardin、Denis Jacquemin、Jérôme Graton、Jean-Yves Le Questel、Michel Evain、Jacques Lebreton、Didier Dubreuil、Jacques Le Pendu、Muriel Pipelier

  DOI：10.1021/jm201368m

  日期：2012.2.9

  We propose here the synthesis and biological evaluation of 0 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.